Blood pressure lowering efficacy of reserpine for primary hypertension

 

Abstract

Background

Many antihypertensive agents exist today for the treatment of primary hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg). Randomised controlled trials have been carried out to investigate the evidence for these agents.There is, for example, strong RCT evidence that thiazides reduce mortality and morbidity. Reserpine has been used as a second-line therapy in some of those trials. However, the dose-related blood pressure reduction with this agent is not known.

Objectives

To investigate the dose-related effect of reserpine on blood pressure, heart rate and withdrawals due to adverse events.

Search methods

The databases CENTRAL, EMBASE, and MEDLINE were searched. We also traced citations in the reference sections of the retrieved studies.

Selection criteria

Included studies were truly randomised controlled trials comparing reserpine monotherapy to placebo or no treatment in patients with primary hypertension.

Data collection and analysis

Methods of randomization and concealment were assessed. Data on blood pressure reduction, heart rate,and withdrawal due to adverse effects were extracted and analysed.

Main results

Four RCTs (N =237) were found that met the inclusion criteria. The overall pooled effect demonstrates a statistically significant systolic blood pressure (SBP) reduction in patients taking reserpine compared to placebo (WMD -7.92, 95% CI -14.05, -1.78). Due to significant heterogeneity across trials, a significant effect in diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) could not be found. The SBP effects were achieved with 0.5 mg/day or greater. However, the dose-response pattern could not be determined because of the small number of trials. Data from the trial that investigated Rauwiloid against placebo was not combined with reserpine data from the remaining three trials. This is because Rauwiloid is a different alkaloid extract of the plant Rauwolfia serpentina and the dose used is not comparable to reserpine. None of the included trials reported withdrawals due to adverse effects.

Authors' conclusions

Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs. However, we could not make definite conclusions regarding the dose-response pattern because of the small number of included trials. More RCTs are needed to assess the effects of reserpine on blood pressure and to determine the dose-related safety profile before the role of this drug in the treatment of primary hypertension can be established.

 

Plain language summary

Reserpine, an old and almost forgotten antihypertensive drug, lowers blood pressure

Reserpine, a root extract of the naturally occurring plant Rauwolfia serpentina, was used in the past as first-line therapy for reducing blood pressure. Nowadays, it is used mainly as a second line agent. This review, which aimed to find and summarize existing evidence from randomised controlled trials, concluded that reserpine is effective in reducing systolic blood pressure as a first-line agent. The degree of this effect was mild to moderate. Because the four included studies did not investigate a wide range of doses, no data was available to infer a dose-related response in blood pressure. Insufficient data was available to evaluate the adverse effects of reserpine therapy.

 

摘要

背景

Reserpine 對原發性高血壓之降壓效果

現今對原發性高血壓(即收縮壓高於140毫米汞柱且/或舒張壓高於90毫米汞柱時，有許多可選擇的降壓藥物。隨機對照試驗研究這些降壓藥物之實證已完成。舉例來說，隨機對照試驗證據強力支持thiazide類藥物可降低死亡率及致病率。在一些隨機對照試驗研究證實reserpine已被用作第二線的降壓藥物。然而，reserpine降低血壓之劑量性相關效果仍是未知的。

目標

目標: 為了調查reserpine降低血壓及心率之劑量性相關相關效果，以及劑量與因不良藥物反應而停藥之關係。

搜尋策略

搜尋文獻所引用的資料庫包括CENTRAL、EMBASE、及MEDLINE。我們同時追蹤所檢索研究之引用文獻的引文。

選擇標準

所擷取的研究都是真正隨機對照控制試驗，比較單一使用reserpine與安慰劑對原發性高血壓之病人治療的效果。

資料收集與分析

我們評估研究內容的隨機分組及雙盲的方法。評估有關降低血壓及心率的效果外，也分析因不良藥物反應而停藥的資訊。

主要結論

四個隨機對照試驗(病人數237人)符合納入標準。在彙總此四研究結果之後，顯示服用reserpine病人收縮壓的降低比安慰劑組有統計學上的意義(加權平均差異(WMD) −7.92, 95%信賴區間−14.05, −1.78)。因為此四組隨機對照試驗間差異性顯著，我們無法得出reserpine比起對照組是否對舒張壓、平均動脈壓、及心率產生統計學上顯著的差異。每天0.5毫克或更大的劑量即可達成對收縮壓的效果。然而，因為這些研究的樣本數太少，我們無法找出劑量性與血壓下降量間的關係。我們也沒有比較Rauwiloid與安慰劑效果組之研究結果併入其他三組研究reserpine的結果。這是因為Rauwiloid是從印度蛇木(Rauwolfia serpentina)萃取出來的一個不同的植物鹼，因此其所使用之劑量無法與reserpine比較。這四組研究均沒有因不良藥物反應而停藥的個案報告。

作者結論

Reserpine可以有效地降低收縮壓，降壓效果大約等同於其他第一線降血壓藥。然而，因為這些研究的樣本數太少，關於劑量性與血壓下降量間的關係，無法得出明確的結論。在確立reserpine對於治療原發性高血壓的角色之前，我們需要更多的隨機對照試驗的結果來評估reserpine降血壓的效果，並確定與劑量性相關的用藥安全概要。

翻譯人

本摘要由臺北榮民總醫院侯冠廷翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

Reserpine這個古老且幾乎被遺忘的藥物可以降低血壓。reserpine是植物印度蛇木(Rauwolfia serpentina)根的萃取物。在過去，它被用做第一線的降血壓藥物。而現在，reserpine主要作為第二線降血壓藥。本篇回顧性評論目標在找出並總結現有的隨機對照試驗的證據。我們得出結論:reserpine能有效降低收縮壓，足以擔當第一線降收縮壓藥物，reserpine降收縮壓的程度是輕度到中度的。因為所納入的四組研究並沒有調查大範圍使用劑量，沒有資料可供推論劑量性與血壓下降量間的關係。同時，我們也沒有充分的資料來評估reserpine的副作用。